Adverse Drug Reactions in Pediatric Oncohematology: A Systematic Review

Adverse drug reactions; Neoplasms; PediatricsReacciones adversas a medicamentos; Neoplasias; PediatríaReaccions adverses als medicaments; Neoplàsies; PediatriaIntroduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6–68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement

Hem estimat la vida: una història sobre l’Alzheimer

Hem estimat la vida és un projecte editorial que neix de la necessitat de preservar els records. És íntim i delicat. Converses a cau d'orella. Està centrat en la història de vida d'un malalt d'Alzheimer, en els moments esborrats de la seva memoria i en com els intentem recuperar.Hem estimat la vida es un proyecto editorial que nace de la necesidad de preservar los recuerdos. Es íntimo y delicado. Conversaciones al oído. Está centrado en la historia de vida de un enfermo de Alzheimer, en los momentos borrados de su memoria y en cómo los intentamos recuperar.Hem estimat la vida is an editorial project born of the need to preserve memories. It is intimate and delicate. Conversations in the ear. It is focused on the life story of an Alzheimer's patient, in the moments erased from his memory and in how we try to recover them

Regulatory framework for advanced therapy medicinal products in Europe and United States

Europe; United States Food and Drug Administration; Legislation and jurisprudenceEuropa; Administración de Alimentos y Medicamentos de los Estados Unidos; Legislación y jurisprudenciaEuropa; Administració d'Aliments i Medicaments dels Estats Units; Legislació i jurisprudènciaAdvanced therapy medicinal products (ATMPs) are a fast-growing field of innovative therapies. The European Union (EU) and the United States (US) are fostering their development. For both regions, ATMPs fall under the regulatory framework of biological products, which determines the legal basis for their development. Sub-classifications of advanced therapies are different between regions, while in EU, there are four major groups, i.e., gene therapy, somatic cell therapy, tissue-engineered therapies, and combined advanced therapies; in US, the sub-classification covers two major groups of products, i.e., gene therapy and cellular therapy. The inclusion criteria that define a gene therapy are equivalent in both regions, and the exclusion criteria are directly related to the indications of the product. In the EU, there is a clear differentiation between cell- and tissue-based products regarding their classification as advanced therapies or coverage by other legal frameworks, whereas in US, there is a broader classification about whether or not these products can be categorized as biologic products. Both in EU and in US, in order to classify a cell- or a tissue-based product as an advanced therapy, it must be ensured that the processing of the cells implies a manipulation that alters their biological characteristics, although the term of manipulation in US differentiates between structural and non-structural cells and tissues. The regulatory terminology used to define ATMPs and their sub-classification reveals some differences between EU and US

Methodological Characteristics of Clinical Trials Supporting the Marketing Authorisation of Advanced Therapies in the European Union

Advanced therapies; Clinical trials; Drug developmentTeràpies avançades; Assaigs clínics; Desenvolupament de fàrmacsTerapias avanzadas; Ensayos clínicos; Desarrollo de fármacosSeveral advanced therapy medicinal products (ATMPs) have been approved in the European Union (EU). The aim of this study is to analyse the methodological features of the clinical trials (CT) that supported the marketing authorization (MA) of the approved ATMPs in the EU. A systematic review of the characteristics of pivotal CT of ATMPs approved in the EU until January 31st, 2021 was carried out. A total of 17 ATMPs were approved and 23 CT were conducted to support the MA (median, 1, range, 1–3). Of those studies, 8 (34.78%) were non-controlled and 7 (30.43%) used historical controls. Only 7 (30.4%) were placebo or active-controlled studies. Among all CT, 21 (91.3%) were open-label and 13 (56.52%) had a single-arm design. To evaluate the primary endpoint, 18 (78.26%) studies used an intermediate and single variable. The median (IQR) number of patients enrolled in the studies was 75 (22–118). To date, ATMPs’ approval in the EU is mainly supported by uncontrolled, single-arm pivotal CT. Although there is a trend toward an adaptive or a life cycle approach, a switch to more robust clinical trial designs is expected to better define the benefit and the therapeutic added value of ATMPs

Resolution test of GOCE satellite data applied to density anomalies at crustal and upper mantle levels

The GOCE satellite mission was devised by the European Space Agency to study the Earthâs gravity field with an unprecedented accuracy using gravity gradient data. The goal of this study is to analyze the resolution in terms of shape, minimum size, and density contrast of anomalous bodies related to geological structures that can be identified from GOCE data. A parametric study is performed by calculating the gravity gradients associated with rectangular prisms with fixed aspect ratio of 9:3:1 and varying the size, burial depth, and density contrast, selecting those structures showing amplitudes and wavelength variations comparable to the accuracy of GOCE data. Results show that the minimum size for crustal anomalies to be resolved is 270 x 90 x 30km for a Dr = 500kg/m3, burial depth of 0km, and a computation height of 255km. A minimum size of 585 x 195 x 65km is required for a body with Dr = 50kg/m3 and 200km burial depth. In addition, the application to the 3D case of a passive continental margin than resembles, in its main general trend, the crustal structure of the NW-Iberia shows that the signal of all gravity gradient components is dominated by the crustal thinning associated with the passive continental margins and the corresponding isostatic response

Measured GFR in murine animal models: review on methods, techniques, and procedures

Animal models; Glomerular filtration rate; Kidney damageModels animals; Taxa de filtració glomerular; Dany renalModelos animales; Tasa de filtración glomerular; Daño renalChronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with increasing rates of morbidity and mortality. Thus, early detection is essential to prevent severe adverse events and the progression of kidney disease to an end stage. Glomerular filtration rate (GFR) is the most appropriate index to evaluate renal function in both clinical practice and basic medical research. Several animal models have been developed to understand renal disease induction and progression. Specifically, murine models are useful to study the pathogenesis of renal damage, so a reliable determination of GFR is essential to evaluate the progression of CKD. However, as in clinical practise, the estimation of GFR in murine by levels of serum/urine creatinine or cystatin-C could not be accurate and needed other more reliable methods. As an alternative, the measurement of GFR by the clearance of exogenous markers like inulin, sinistrin, 51Cr-EDTA, 99mTc-DTPA, 125I-iothalamate, or iohexol could be performed. Nevertheless, both approaches—estimation or measurement of GFR—have their limitations and a standard method for the GFR determination has not been defined. Altogether, in this review, we aim to give an overview of the current methods for GFR assessment in murine models, describing each methodology and focusing on their advantages and limitations.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work is supported by funding from the Instituto de Salud Carlos III with the following grants: AERR is a recipient of a contract from the Sara Borrell programme (C21/00142) and STT of PFIS FI20/00147

Síndrome metabólico en personal de enfermería

Objectives: To estimate the prevalence of metabolic syndrome (MS) in female nurses in the Hospital Juan A. Fernandez (HJAF), Buenos Aires, Argentina, and to determine whether work, rest, diet, and health, are predictive of it.Materials and methods: For the first objective, a descriptive, observational and cross-sectional study was conducted, and for the second, a multivariate cross-sectional observational multivariate analysis was made comparing independent samples. A total of 192 nurses were studied between October 2008 and March 2009. They completed a questionnaire that include indicators that could be predictors of MS. Anthropometric measurements, including blood pressure were taken, was well as a blood sample to analyze fasting glucose, HDL-C and plasma triglycerides.Results: It was found that 35% and 41% of nurses were overweight and obese, respectively. A total of 92% had centro-abdominal obesity. The prevalence of MS found was 33.3% (95%CI, 26.7 to 40.5). Those who had this disease were between 53±9 years. Statistically significant differences were found in the bivariate analysis between MS and the variables, age, length of service, time worked during night shift, and academic studies.Conclusions: The prevalence of MS was 64/192 in HJAF nurses (33.3% I 95%CI, 26.7-40.5). There were no statistically significant differences with the indicators of, age, “time worked during night shift”, and “studies”. These results suggest that age is the most important variable in predicting the onset of MS in the population of nurses.Objetivos: Estimar la prevalencia de síndrome metabólico (SM) entre las enfermeras del Hospital Juan A. Fernández (HJAF) y determinar si trabajo, descanso, dieta y estado de salud son sus predictores.Material y métodos: Para el primer objetivo, el diseño del estudio es descriptivo, observacional y transversal. Para el segundo, comparación de muestras independientes, multivariable, observacional y transversal. Se estudió a 192 enfermeras entre octubre de 2008 y marzo de 2009. Se les realizó una encuesta autoaplicable con indicadores que podrían ser predictores de SM. Se tomaron mediciones antropométricas, presión arterial y extracción sanguínea para analizar glucemia en ayunas, colesterol unido a lipoproteínas de alta densidad y triglicéridos plasmáticos.Resultados: El 35 y el 41% del personal de enfermería tenían sobrepeso y obesidad respectivamente. Un 92% del total tenía obesidad centroabdominal. La prevalencia de SM hallada es del 33,3% (intervalo de confianza del 95%, 26,7%-40,5%). Las afectas de SM tenían una media de edad de 53 ± 9 años. En el análisis bivariable se encontraron diferencias estadísticamente significativas entre el SM y las variables edad, tiempo de ejercicio profesional, tiempo trabajado en turno de noche y estudios realizados.Conclusiones: La prevalencia de SM de enfermeras del HJAF fue de 64/192 (33,3%; intervalo de confianza del 95%, 26,7%-40,5%). Frente a la edad, los indicadores tiempo trabajado durante turno noche y estudios realizados no muestran diferencias estadísticamente significativas. Estos resultados indicarían que la edad es la variable más relevante para predecir la aparición de SM en la población de enfermeras

Spontaneously Reported Adverse Drug Reactions and Their Description in Hospital Discharge Reports: A Retrospective Study

Reacció adversa al fàrmac; Informe d'alta hospitalària; FarmacovigilànciaReacción adversa al medicamento; Informe de alta hospitalaria; FarmacovigilanciaAdverse drug reaction; Hospital discharge report; PharmacovigilanceThe inclusion of spontaneously reported adverse drug reactions (ADRs) in hospital discharge reports was examined, in addition to the factors associated with their inclusion, the resulting therapeutic decisions, and any recommendations made upon patient discharge regarding the suspected offending drugs. ADRs that were spontaneously reported during 2017 and 2018 to the pharmacovigilance program were retrospectively analyzed. Information regarding patient characteristics, drug treatments, and ADRs was collected from the ADR notifications and from patient electronic medical records. The dependent variable was the mentioning of ADRs in the discharge reports, while characteristics of the ADRs, pharmacovigilance causality algorithms, and some of the suspected drugs themselves were the independent variables during bivariant analysis. A total of 286 reports of suspected ADRs from 271 patients (50.2% female; 77% adults) were included. Information regarding the ADRs was present in the discharge reports for 238 reports (83.2%); the ADR seriousness and the lack of potential alternative causes were the only associated factors. Withdrawal or withdrawal and substitution by an alternative drug were the most common therapeutic decisions, although often no recommendation was made. Overall, there is still room for improvement in terms of including information related to ADRs in hospital discharge reports.This research received no external funding

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

Heterologous vaccination; Neutralisation; SARS-CoV-2Vacunación heteróloga; Neutralización; SARS-CoV-2Vacunació heteròloga; Neutralització; SARS-CoV-2Background The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49–5956·71) in the IG and 7298·22 BAU/mL (6739·41–7903·37) in the CG (p 1:100 at day 180 (19% and 22%, respectively). Interpretation Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180.Funded by Instituto de Salud Carlos III (ISCIII)

Inappropriate prescribing to the oldest old patients admitted to hospital : prevalence, most frequently used medicines, and associated factors

Scientific evidence on treatments of chronic diseases in patients 85 years old or older is very limited, as is available information on inappropriate prescription (IP) and its associated factors. The study aimed to describe medicine prescription, potentially inappropriate medicines (PIM) and potentially prescribing omissions (PPO) and their associated factors on this population. In the context of an observational, prospective and multicentric study carried out in elderly patients admitted to seven Spanish hospitals for a year, a sub-analysis of those aged 85 years and over was performed. To assess PIMs, the Beers and STOPP criteria were used, and to assess PPOs, the START and the ACOVE-3 criteria were used. To assess factors associated with IP, a multivariate logistic regression analysis was performed. Patients were selected randomly every week on consecutive days from the hospitalization lists. A total of 336 patients were included in the sub-analysis with a median (Q1-Q3) age of 88 (86-90) years. The median medicines taken during the month prior to admission was 10 (7-13). Forty-seven point two per cent of patients had at least one Beers-listed PIM, 63.3% at least one STOPP-listed PIM, 53.6% at least one START-listed PPO, and 59.4% at least one ACOVE-3-listed PPO. Use of benzodiazepines in patients who are prone to falls (18.3%) and omission of calcium and vitamin D supplements in patients with osteoporosis (13.3%) were the most common PIM and PPO, respectively. The main factor associated with the Beers-listed and the STOPP-listed PIM was consumption of 10 or more medicines (OR = 5.7, 95% CI 1.8-17.9 and OR = 13.4, 95% CI 4.0-44.0, respectively). The main factors associated with the START-listed PPO was a non-community dwelling origin (OR 2.3, 95% CI 1.0-5.0), and multimorbidity (OR1.8, 95% CI 1.0-3.1). Prescribed medicines and PIM and PPO prevalence were high among patients 85 years and over. Benzodiazepine use in those who are prone to falls and omission of calcium and vitamin D in those with osteoporosis were the most frequent PIM and PPO, respectively. Factors associated with PIM and PPO differed with polypharmacy being the most important factor associated with PIM. The online version of this article (doi:10.1186/s12877-015-0038-8) contains supplementary material, which is available to authorized users